CN102349998A - Hydrophobic anticancer medicinal preparation on basis of exosome - Google Patents
Hydrophobic anticancer medicinal preparation on basis of exosome Download PDFInfo
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- CN102349998A CN102349998A CN 201110321620 CN201110321620A CN102349998A CN 102349998 A CN102349998 A CN 102349998A CN 201110321620 CN201110321620 CN 201110321620 CN 201110321620 A CN201110321620 A CN 201110321620A CN 102349998 A CN102349998 A CN 102349998A
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Abstract
The invention relates to hydrophobic anticancer medicinal preparation on the basis of an exosome. A carrier used by the medicinal preparation provided by the invention is the exosome and is derived from body fluids such as the spittle, the blood and the like of an animal body, and a cell culture fluid. The exosome is derived from the animal body per se, has indubitable biocompatibility, simultaneously has a lipid bilayer similar to a cell membrane, and has the capability of encapsulating and carrying a hydrophobic anticancer medicine. The carrier used by the medicinal preparation provided by the invention has uniform grain diameters which are approximately about 100 nm, and is derived from the animal body per se synchronously, and the long circulation of the carrier in the animal body is beneficial, thereby greatly improving the bioavailability of a medicine. A drawing is the scanning electron microscope picture of the exosome.
Description
Technical field
The present invention relates to a kind of hydrophobic anticancer drug preparation of body of secreting in addition for the basis; The employed carrier of preparation is the outer body of secreting that derives from animal body; Can deliver all hydrophobic drugs, specifically be mentioned to the delivery of medicines such as amycin, aspirin, temozolomide, paclitaxel.
Background technology
The active substance that is got by high-flux medicaments sifting has 40% to be hydrophobic approximately at present.Hydrophobic drug is little because of its dissolubility in water, medicine is difficult to reach the required least concentration of treatment, be difficult to by body absorb, bioavailability is low, limited clinical practice, and be difficult to realize the variation of dosage form.In the research of recent new drug development, it is in order to improve bioavailability and water solublity that 41% workload is arranged.The dissolubility that strengthens hydrophobic drug is of great practical significance and researching value, is the medical chemistry problem demanding prompt solution.Through some carrier parcel, is a kind of efficient ways of hydrophobic drug being carried out solubilising with hydrophobic drug.
Bag for hydrophobic drug carries several carriers below main the application now: liposome, and cyclodextrin, surfactant micella, polymer micelle etc., though obtained certain effect, biocompatibility still is the problem that these several carriers can't be avoided.And secrete the problem that body can well solve biocompatibility outward as what derive from organism itself.
The secretion of secreting body is outward knitted in the erythrocytic maturation process at research network in 1987 by Johnstone etc. the earliest and is found.In the supernatant of In vitro culture sheep reticulocyte,, can collect the capsule property vesicle of diameter 60nm, contain the after birth structure of emitting in the reticulocyte maturation process in the vesicle through behind the centrifugal 90min of 100000g.Johnstone etc. secrete body outward with these nano level vesicle called afters, and think that outer release of secreting body is a kind of adjusting approach that discharges " unnecessary " memebrane protein in the cell in the reticulocyte maturation process.Find to have various kinds of cell can discharge this nanometer bubble subsequently, comprise epithelial cell, mastocyte, fibroblast, platelet, tumor cell, antigen presenting cell, hepatocyte and enterocyte.The biology process of producing into of secreting body outward comprise endosome to endogenous budding generate many vesicles body, many vesicles body merges with after birth and it is discharged into these two steps outside the born of the same parents.
The research of secreting body outward mainly rests on disease surveillance and the tumor vaccine now, and for it as the research of pharmaceutical carrier also seldom, related patent U.S. Patent No. does not also have.
Summary of the invention
The object of the present invention is to provide a kind of hydrophobic anticancer drug preparation of body of secreting in addition for the basis.
Principle of the present invention is that the hydrophobic region that utilizes the outer lipid bilayer of secreting body to exist wraps a year hydrophobic anticancer drug, thereby prepares hydrophobic anti-cancer drug preparation.
The hydrophobic anticancer drug preparation of secreting body for the basis beyond a kind of of the present invention, the employed carrier of pharmaceutical preparation be for secreting body outward, and it derives from the body fluid and the cell culture fluids such as saliva, blood of animal body; The hydrophobic anticancer drug suppressed by vector wraps and carries.
The carrier of said pharmaceutical preparation; From the body fluid or cell culture fluid of animal; Method or ExoQuick solution separating method through centrifuging or magnetic bead surfaces coated antibody; Obtain the outer body of secreting of emiocytosis; And will secrete body adding phosphate buffer outward; Phosphate buffer is the 1/100-1/10 of former body fluid or cell culture fluid, obtains the outer liquid solution of secreting.
Adopt the hydrophobic anticancer drug preparation of body of secreting in addition of the present invention for the basis; Hydrophobic anticancer drug is joined outer secreting in the liquid solution; Additional proportion is 1: 10-1000 (g/ml); Drug precipitation is in the bottom; Agitating solution hatching 0.5-24 hour; Get supernatant, obtain wrapping the outer liquid solution of secreting of medicine carrying thing, the outer liquid solution of secreting with this bag medicine carrying thing is used as pharmaceutical preparation again.
Secrete the hydrophobic anticancer drug preparation of body for the basis beyond this, used carrier is for secreting body outward, and it derives from animal body itself; The hydrophobic drug suppressed by vector wraps and carries.
Advantage of the present invention: secrete the hydrophobic anticancer drug preparation of body beyond this for the basis, its good biocompatibility, animal body inner blood circulation time is long, improves the bioavailability of medicine greatly.
Description of drawings
Fig. 1: the sem photograph of secreting body outward.
The specific embodiment
Through example the present invention is further set forth below.
Embodiment 1:
1. get rat blood 2ml, prepare the outer body of secreting of emiocytosis through centrifuging, and will secrete body outward and add 20 μ l phosphate buffers, the volume of phosphate buffer is 1/100 of a former blood volume, obtains the outer liquid solution of secreting.
2. 2 μ g amycin medicines are added outer secreting in the liquid solution, medicine is 1: 10 (mg/ml) with secreting the liquid solution ratio outward, and drug precipitation is in the bottom; Agitating solution hatching 0.5 hour; Get supernatant, obtain wrapping the outer liquid solution of secreting of medicine carrying thing, the outer liquid solution of secreting with this bag medicine carrying thing is used as pharmaceutical preparation again.
With the amycin of same amount with secrete the pharmaceutical preparation that the body bag carries amycin outward and be injected into respectively in the rat body; Secreting the blood circulation time that the body bag carries the pharmaceutical preparation of amycin outward is 50 hours; The blood circulation time of amycin is 4 hours, secretes the blood circulation time that blood circulation time that the body bag carries the pharmaceutical preparation of amycin is significantly higher than amycin outward.
Embodiment 2:
1. get rat blood 2ml, prepare the outer body of secreting of emiocytosis through the method for magnetic bead surfaces coated antibody, and will secrete body outward and add 200 μ l phosphate buffers, the volume of phosphate buffer is 1/10 of a former blood volume, obtains the outer liquid solution of secreting.
2. 0.2 μ g amycin medicine is added outer secreting in the liquid solution; Medicine is 1: 1000 (mg/ml) with secreting the liquid solution ratio outward; Drug precipitation is in the bottom; Agitating solution hatching 24 hours; Get supernatant; Obtain wrapping the outer liquid solution of secreting of medicine carrying thing, the outer liquid solution of secreting with this bag medicine carrying thing is used as pharmaceutical preparation again.
With the amycin of same amount with secrete the pharmaceutical preparation that the body bag carries amycin outward and be injected into respectively in the rat body; Secreting the blood circulation time that the body bag carries the pharmaceutical preparation of amycin outward is 50 hours; The blood circulation time of amycin is 4 hours, secretes the blood circulation time that blood circulation time that the body bag carries the pharmaceutical preparation of amycin is significantly higher than amycin outward.
Embodiment 3:
1. get rat blood 2ml, obtain the outer body of secreting of emiocytosis through the ExoQuick formulations prepared from solutions, and will secrete body outward and add 100 μ l phosphate buffers, the volume of phosphate buffer is 1/20 of a former blood volume, obtains the outer liquid solution of secreting.
2. 1 μ g amycin medicine is added outer secreting in the liquid solution, medicine is 1: 100 (mg/ml) with secreting the liquid solution ratio outward, and drug precipitation is in the bottom; Agitating solution hatching 12 hours; Get supernatant, obtain wrapping the outer liquid solution of secreting of medicine carrying thing, the outer liquid solution of secreting with this bag medicine carrying thing is used as pharmaceutical preparation again.
With the amycin of same amount with secrete the pharmaceutical preparation that the body bag carries amycin outward and be injected into respectively in the rat body; Secreting the blood circulation time that the body bag carries the pharmaceutical preparation of amycin outward is 50 hours; The blood circulation time of amycin is 4 hours, secretes the blood circulation time that blood circulation time that the body bag carries the pharmaceutical preparation of amycin is significantly higher than amycin outward.
Embodiment 4:
1. get rat blood 2ml, obtain the outer body of secreting of emiocytosis through the ExoQuick formulations prepared from solutions, and will secrete body outward and add 100 μ l phosphate buffers, the volume of phosphate buffer is 1/20 of a former blood volume, obtains the outer liquid solution of secreting.
2. 10 μ g aspirin medicines are added outer secreting in the liquid solution; Medicine is 1: 10 (mg/ml) with secreting the liquid solution ratio outward; Drug precipitation is in the bottom; Agitating solution hatching 0.5 hour; Get supernatant; Obtain wrapping the outer liquid solution of secreting of medicine carrying thing, the outer liquid solution of secreting with this bag medicine carrying thing is used as pharmaceutical preparation again.
With the aspirin of same amount with secrete the pharmaceutical preparation that the body bag carries aspirin outward and be injected into respectively in the rat body; Secreting the blood circulation time that the body bag carries the pharmaceutical preparation of aspirin outward is 46 hours; The blood circulation time of aspirin is 5 hours, secretes the blood circulation time that blood circulation time that the body bag carries the pharmaceutical preparation of aspirin is significantly higher than aspirin outward.
Embodiment 5:
1. get rat blood 2ml, obtain the outer body of secreting of emiocytosis through the ExoQuick formulations prepared from solutions, and will secrete body outward and add 100 μ l phosphate buffers, the volume of phosphate buffer is 1/20 of a former blood volume, obtains the outer liquid solution of secreting.
2. 10 μ g temozolomide medicines are added outer secreting in the liquid solution; Medicine is 1: 10 (mg/ml) with secreting the liquid solution ratio outward; Drug precipitation is in the bottom; Agitating solution hatching 24 hours; Get supernatant; Obtain wrapping the outer liquid solution of secreting of medicine carrying thing, the outer liquid solution of secreting with this bag medicine carrying thing is used as pharmaceutical preparation again.
With the temozolomide of same amount with secrete the pharmaceutical preparation that the body bag carries the temozolomide outward and be injected into respectively in the rat body; Secreting the blood circulation time that the body bag carries temozolomide's pharmaceutical preparation outward is 40 hours; Temozolomide's blood circulation time is 6 hours, secretes the blood circulation time that blood circulation time that the body bag carries temozolomide's pharmaceutical preparation is significantly higher than the temozolomide outward.
Embodiment 6:
1. get rat blood 2ml, obtain the outer body of secreting of emiocytosis through the ExoQuick formulations prepared from solutions, and will secrete body outward and add 100 μ l phosphate buffers, the volume of phosphate buffer is 1/20 of a former blood volume, obtains the outer liquid solution of secreting.
2. 10 μ g taxol drug are added outer secreting in the liquid solution, medicine is 1: 10 (mg/ml) with secreting the liquid solution ratio outward, and drug precipitation is in the bottom; Agitating solution hatching 12 hours; Get supernatant, obtain wrapping the outer liquid solution of secreting of medicine carrying thing, the outer liquid solution of secreting with this bag medicine carrying thing is used as pharmaceutical preparation again.
With the paclitaxel of same amount with secrete the pharmaceutical preparation that the body bag carries paclitaxel outward and be injected into respectively in the rat body; Secreting the blood circulation time that the body bag carries the pharmaceutical preparation of paclitaxel outward is 42 hours; The blood circulation time of paclitaxel is 4.8 hours, secretes the blood circulation time that blood circulation time that the body bag carries the pharmaceutical preparation of paclitaxel is significantly higher than paclitaxel outward.
Claims (4)
1. secrete the hydrophobic anticancer drug preparation of body beyond one kind for the basis; It is characterized in that: the form of carrier loaded medicine is adopted in pharmaceutical preparation; The employed carrier of preparation is for secreting body outward, and it derives from the culture fluid of body fluid and cell of the saliva that comprises animal body, blood.
2. pharmaceutical preparation according to claim 1 is characterized in that said medicine carrying comprises all hydrophobic anticancer drug of amycin, aspirin, temozolomide, paclitaxel, daunorubicin, colchicine or vincristine.
3. pharmaceutical preparation according to claim 1; It is characterized in that said carrier is: from the body fluid or cell culture fluid of animal; Method or ExoQuick solution separating method through centrifuging or magnetic bead surfaces coated antibody; Obtain the outer body of secreting of emiocytosis; And will secrete body adding phosphate buffer outward; Phosphate buffer is the 1/100-1/10 of former body fluid or cell culture fluid, obtains the outer liquid solution of secreting.
4. like pharmaceutical preparation as described in claim 1 or 2; It is characterized in that: hydrophobic anticancer drug is joined outer secreting in the liquid solution; Additional proportion is 1: 10-1000 (mg/ml); Drug precipitation is in the bottom; Agitating solution hatching 0.5-24 hour; Get supernatant, obtain wrapping the outer liquid solution of secreting of medicine carrying thing, the outer liquid solution of secreting with this bag medicine carrying thing is used as pharmaceutical preparation again.。
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Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103468642A (en) * | 2013-09-23 | 2013-12-25 | 山西大学 | Method for separating exosome from cell culture medium |
| CN105849554A (en) * | 2013-10-24 | 2016-08-10 | 新加坡科技研究局 | Exosome recovery methods with low molecular weight organic zwitterions |
| CN106974938A (en) * | 2017-04-14 | 2017-07-25 | 南京盖斯夫医药科技有限公司 | A kind of the excretion body and its pharmaceutical preparation in the mesenchymal stem cells MSCs source with antihepatocarcinoma effect |
| CN107375234A (en) * | 2017-07-10 | 2017-11-24 | 武汉大学 | A kind of multifunctional carrier and preparation method and application based on cell source vesica in body fluid |
| WO2019077534A1 (en) | 2017-10-18 | 2019-04-25 | Tubitak | An exosomal therapeutic carrier production method and an exosomal therapeutic carrier properly obtained with this method |
| CN109675032A (en) * | 2019-02-13 | 2019-04-26 | 南通大学 | The drug and application thereof for the chemotherapeutic composition that optothermal material and excretion body mediate |
| CN110343664A (en) * | 2018-04-03 | 2019-10-18 | 中国人民解放军军事科学院军事医学研究院 | The method for extracting excretion body and excretion body protein |
| CN110652492A (en) * | 2019-09-18 | 2020-01-07 | 浙江大学 | Drug-loaded exosome, application thereof and liver disease drug |
| CN111195240A (en) * | 2018-11-19 | 2020-05-26 | 重庆大学 | Application of exosome in preparing anti-infective medicament |
| CN112118866A (en) * | 2018-03-23 | 2020-12-22 | 科迪亚克生物科学公司 | Extracellular vesicles comprising STING agonists |
| CN114376986A (en) * | 2022-02-25 | 2022-04-22 | 南京中医药大学 | Bionic nanoparticle for homologous recombination exosome multi-drug delivery and preparation method and application thereof |
| CN115350282A (en) * | 2022-07-29 | 2022-11-18 | 维思克思生物科技(武汉)有限公司 | Medicine-carrying exosome targeting liver cancer, rapid preparation method and application thereof |
-
2011
- 2011-10-20 CN CN 201110321620 patent/CN102349998A/en active Pending
Non-Patent Citations (3)
| Title |
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| 《Molecular Therapy》 20100622 Dongmei Sun等 《A Novel Nanoparticle Drug Delivery System:The Anti-inflammatory Activity of Curcumin Is Enhanced When Encapsulated in Exosomes》 第1606－1614页 1－4 第18卷, 第9期 * |
| 《中国临床康复》 20060815 张红菱等 《一种新的纳米级细胞来源囊泡外泌体的特征》 第128－130页 1－4 第10卷, 第30期 * |
| 《肿瘤》 20110630 杨子楠等 《外泌体在肿瘤发展中的研究进展》 第565－569页 1－4 第31卷, 第6期 * |
Cited By (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103468642A (en) * | 2013-09-23 | 2013-12-25 | 山西大学 | Method for separating exosome from cell culture medium |
| CN105849554A (en) * | 2013-10-24 | 2016-08-10 | 新加坡科技研究局 | Exosome recovery methods with low molecular weight organic zwitterions |
| CN106974938B (en) * | 2017-04-14 | 2020-06-23 | 吉林市汇融再生医学有限公司 | Exosome with anti-liver cancer effect and derived from mesenchymal stem cells and pharmaceutical preparation of exosome |
| CN106974938A (en) * | 2017-04-14 | 2017-07-25 | 南京盖斯夫医药科技有限公司 | A kind of the excretion body and its pharmaceutical preparation in the mesenchymal stem cells MSCs source with antihepatocarcinoma effect |
| CN107375234A (en) * | 2017-07-10 | 2017-11-24 | 武汉大学 | A kind of multifunctional carrier and preparation method and application based on cell source vesica in body fluid |
| CN107375234B (en) * | 2017-07-10 | 2021-03-05 | 武汉大学 | Multifunctional carrier based on cell-derived vesicles in body fluid and preparation method and application thereof |
| WO2019077534A1 (en) | 2017-10-18 | 2019-04-25 | Tubitak | An exosomal therapeutic carrier production method and an exosomal therapeutic carrier properly obtained with this method |
| CN112118866A (en) * | 2018-03-23 | 2020-12-22 | 科迪亚克生物科学公司 | Extracellular vesicles comprising STING agonists |
| CN110343664A (en) * | 2018-04-03 | 2019-10-18 | 中国人民解放军军事科学院军事医学研究院 | The method for extracting excretion body and excretion body protein |
| CN111195240A (en) * | 2018-11-19 | 2020-05-26 | 重庆大学 | Application of exosome in preparing anti-infective medicament |
| CN109675032A (en) * | 2019-02-13 | 2019-04-26 | 南通大学 | The drug and application thereof for the chemotherapeutic composition that optothermal material and excretion body mediate |
| CN110652492A (en) * | 2019-09-18 | 2020-01-07 | 浙江大学 | Drug-loaded exosome, application thereof and liver disease drug |
| CN114376986A (en) * | 2022-02-25 | 2022-04-22 | 南京中医药大学 | Bionic nanoparticle for homologous recombination exosome multi-drug delivery and preparation method and application thereof |
| CN115350282A (en) * | 2022-07-29 | 2022-11-18 | 维思克思生物科技(武汉)有限公司 | Medicine-carrying exosome targeting liver cancer, rapid preparation method and application thereof |
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Application publication date: 20120215 |